An Episcopal (Anglican) Chaplain in the Saint Luke's Health System of Kansas City, reflecting on work and faith and life. NOTA BENE: my opinions are my own and do not represent the Episcopal Church or the Saint Luke's Health System.

Tuesday, October 02, 2007

Problems Basing Human Studies on Animal Studies

A few days ago I was listening to BBC World Service on my computer, when I caught just the end of a news report. What caught my attention was a statement from a British medical researcher that went something like this: “We base our medical studies on humans on our studies on animals. But, if the studies on animals don’t follow the same standards, don’t have the same quality, then how can we trust the results? Is this what we’re basing our human subject research on?”

Well, I went digging, but I couldn’t find the news report. (If someone out there can, I’ll be happy to give a more accurate quote and appropriate credit.) However, I did find this. This is a study by Luciano E Mignini, MD and Khalid S Khan, M.Sc. and a Member of the Royal College of Obstetrics and Gyenecology, titled, “Methodological quality of systematic reviews of animal studies: a survey of reviews of basic research.” The article was published at BMC Medical Research Methodology, an online journal.

You can get a sense of the concern the researchers were addressing from their “Backgrounds” section:

In the development of new health technologies, it is widely held that drugs or procedures should first be assessed in animal models before proceeding to clinical trials in humans. High quality systematic reviews provide unbiased overviews of the available evidence. There have been calls for application of this approach in basic research, particularly in animal research, to better understand biological plausibility and to translate findings of basic research to the bedside. Cumulative assessment of emerging evidence in animal research can help rationalize human clinical trials. The idea that these experiments impact future human studies is well recognised, but lack of systematic review of this evidence can lead to a sort of research bias that has seldom been previously considered explicitly. The link (or lack of appreciation of a link) between animal and human studies is illustrated by the case of nimodipine in focal cerebral ischemia; it has become clear from systematic review of animal experiments that there was no convincing evidence to substantiate the decision to perform trials with nimodipine in humans Because the initial animal studies were not evaluated systematically; human trials of nimodipine proceeded at significant cost and potential human risk despite a lack of clear scientific rationale. The extent and the quality of systematic reviews of animal studies is unknown. The aim of this study was to assess the methodological features of such systematic reviews.

To translate: when preparing to do medical research involving human subjects, scientists review the literature for reports of relevant research on animal subjects. Part of what they look for is reviews of research on animal subjects. However, research studies on animals haven’t been subject to the same qualitative review that is common in studies on human subjects; and, as a result, decisions can be made based on animal studies that aren’t in fact well done. Therefore, they decided to review a large group of animal studies for standards of good research practice that they felt would be necessary for good human subject research. In describing their own methodology, they list the standards and procedures they’re looking for.

The results of their review?

From 4749 citations initially identified, 1517 were considered potentially relevant and their full manuscripts were evaluated. Among these, there were only 30 (1.9% of 1517) reviews of animal studies that met our selection criteria. The reviews summarised studies of animals including cat, cow, horse, dog, mouse, nonhuman primate, rabbit, rat, sheep and swine amongst others. The ranges of topics included cardiology, dentistry, gynaecology, immunology, neonatology, obstetrics, oncology, toxicology and urology amongst others….

There next paragraph goes on to detail the standards by which significant portions of those 1517 studies fell short.

Now, this is an important issue in medical ethics. As the authors note, studies involving human subjects are determined to worth pursuing, both in terms of results and in terms of benefits outweighing risks, based largely on studies in animals. However, the assumption is that those animal studies are well done, and meet sufficient standards for quality. If those studies do not meet sufficient standards, they mislead researchers, wasting money and time with no benefit to patients. The authors citation of the nimodipine studies is a case in point.

Moreover, not only are such poor studies not sufficient grounds for moving forward to human studies, they are not adequate justification for any risks and suffering for the animals. After all, it is a recognized principle in human subject research that a study that will not produce usable results by definition places those human subjects at inappropriate risk. If these animal studies are not producing usable results, they put the animals at a risk that is at least wasteful, and is demonstrably immoral.

I am also concerned about this study because it brings me back to a favorite soapbox: the tendency for any research study that shows progress in a disease that we fear to show up in the evening news. There is always the caveat that “it will be years before we know whether this will result in a new treatment;” but by that point the damage is done. The public has been told of a study result, and told that the result was hopeful. If the study is good, that may well be in question: it is a long way from an animal study to a useful treatment for humans. If, on the other hand, the study is poor it is indeed false hope, perpetrated by haste. Particularly where there are people suffering with diseases for which we currently have little to offer, bad studies are mercy delayed and distracted; and indiscriminate publication in the broadcast media is little better.

I’m sure others will be looking at this article with their own reviews and arguments. I think that will be good, and will move medical research forward. However, in the meantime we need to take animal studies with a grain of salt, both those in research and we in the larger community. We trust – we can only trust - that researchers will carefully evaluate animal studies when they seek justification to move forward with human subjects. We need whenever we can to express our own concerns that those studies be done according to the highest research standards.

3 comments:

SABRE Research UK
said...

The quote was from Professor Ian Roberts of the London School of Hygeine and Tropical Medicine and Dr Malcolm Macleod of Edinburgh University. The study referred to was published in Trends in Neurosciences 'How can we improve the pre-clinical development of drugs for stroke?' Pages 433-439Emily Sena, H. Bart van der Worp, David Howells and Malcolm Macleod. You may also want to view this paper: 'Comparison of treatment effects between animal experiments and clinical trials: systematic review' Perel et al. http://www.bmj.com/cgi/content/abstract/bmj.39048.407928.BEv1For further information visit: www.SABRE.org.uk

Well-written and thoughtful. Good to know of other chaplain bloggers here. I read the article about you in Healing Spirit magazine and am always glad to know of others who are making their mark in the chaplaincy world. Thank you.